title: Cell-cycle regulated transcription associates with DNA replication timing in yeast and human.
abstract: BACKGROUND
  Eukaryotic DNA replication follows a specific temporal program, with some genomic regions consistently replicating earlier than others, yet what determines this program is largely unknown. Highly transcribed regions have been observed to replicate in early S-phase in all plant and animal species studied to date, but this relationship is thought to be absent from both budding yeast and fission yeast. No association between cell-cycle regulated transcription and replication timing has been reported for any species.
  
  
  RESULTS
  Here I show that in budding yeast, fission yeast, and human, the genes most highly transcribed during S-phase replicate early, whereas those repressed in S-phase replicate late. Transcription during other cell-cycle phases shows either the opposite correlation with replication timing, or no relation. The relationship is strongest near late-firing origins of replication, which is not consistent with a previously proposed model—that replication timing may affect transcription—and instead suggests a potential mechanism involving the recruitment of limiting replication initiation factors during S-phase.
  
  
  CONCLUSIONS
  These results suggest that S-phase transcription may be an important determinant of DNA replication timing across eukaryotes, which may explain the well-established association between transcription and replication timing.
authors.forename: Hunter B
authors.initials: HB
authors.lastname: Fraser
mesh_terms: D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D042522:DNA Replication Timing; D005786:Gene Expression Regulation; D006801:Humans; D004718:Saccharomycetales / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics; D014158:Transcription, Genetic; D015003:Yeasts / Q000235:genetics*